3-Methyl-7-alkylxanthines are important intermediates for pharmaceuticals. For example, 3,7-dimethylxanthine (theobromine) is an important intermediate for 1-(5-oxohexyl)-3,7-dimethylxanthine (pentoxyfylline), and 3-methyl-7-propylxanthine is an important intermediate for 1-(5-oxohexyl)-3-methyl-7-propylxanthine (propentophylline).
3,7-Dimethylxanthine has conventionally been produced by extraction from cocoa beans or by synthesis from 3-methylurea.
Propentophylline, which is useful as a drug for treating cerebrovascular disorders, has generally been synthesized by the introduction of a 5-oxohexyl group into 3-methyl-7-propylxanthine as disclosed in JP-B-52-33120 (the term "JP-B" as used herein means an "examined Japanese patent publication"). The starting material 3-methyl-7-propylxanthine can be synthesized through various chemical processes. A typical example is a process comprising treating 1,3-dimethyl-7-propylxanthine with an alkali to obtain 4-methylamino-5-methylcarbamoyl-1-propylimidazole, which is reacted with urea to obtain N-methyl-N-(5-methylcarbamoyl-1-propylimidazol-4-yl)urea, followed by cyclization as disclosed in JP-A-1-180883 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). However, these known chemical synthesis processes have many problems in their application to industrial production, including involvement of very complicated steps. Therefore, it is desirable to develop a simpler process for synthesizing 3-methyl-7-propylxanthine.
Further, microbial techniques for synthesizing 3,7-dimethylxanthine have been studied. For example, converting 1,3,7-trimethylxanthine (caffeine) into 3,7-dimethylxanthine by using a microorganism capable of assimilating caffeine or a mutant strain thereof was suggested in Hoope-Seyler's Z. Physiolo. Chem., Vol. 358, p. 807 (1977), JP-B-4-12117, and EP-A-0509834.
However, microbial synthesis of a 3-methyl-7-alkylxanthine other than 3,7-dimethylxanthine is unknown. In addition, the known microbial processes for synthesizing 3,7-dimethylxanthine are still unsatisfactory for carrying out on an industrial scale from the standpoint of conversion efficiency, and the like.